Published papers

There is increasing evidence to suggest that the expression of many molecules in the lateral wall of the cochlea plays an important role in noise-induced stress responses. In this study, activation of the nuclear transcription factor nuclear factor-kappa B (NF-κB) was investigated in the cochlea of mice treated with intense noise exposure (4 kHz, octave band, 124 dB, for 2 h). The present noise exposure led to remarkable auditory brainstem response threshold shifts and cochlear damage on surface preparations. To assess the effects of noise exposure on NF-κB/DNA binding activity in the cochlea, we prepared nuclear extracts from the cochlea at different time points after noise exposure and carried out an electrophoretic mobility shift assay using a probe specific to NF-κB. NF-κB/DNA binding was significantly enhanced in the cochlea 2-6 h after noise exposure and returned to basal levels after 12 h. Supershift analysis using antibodies against p65 and p50 proteins, which are components of NF-κB, demonstrated that enhancement of NF-κB/DNA binding was at least in part due to nuclear translocation of p65. An immunohistochemical study also showed that nuclear translocation of both p65 and p50 was observed in the lateral wall after noise exposure and that there may be a possible close association between p65 and enhanced inducible nitric oxide synthase expression. These results suggest that NF-κB may have a detrimental role in the response to acoustic overstimulation in the cochlea of mice.

Conductive hearing impairiment induced by otosclerosis, a typical otological disease, can be dramatically improved by surgery. This review introduces an original surgical procedure using a ceramic apatite implant, and summarizes successful surgical results involving 160 otosclerotic ears.

Head and neck squamous cell carcinoma is the sixth most common type of neoplasm worldwide, but its prognosis has not improved significantly in recent years. Therefore, efforts need to be intensified to gain a better understanding of this disease and develop novel treatment strategies. Inhibition of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol: inositol transferase by inostamycin, an antibiotic isolated from Streptomyces sp. MH816-AF15, induces G1 cell cycle arrest accompanied by a decrease in cyclin D1 and phosphorylated RB protein levels, along with suppression of in vitro invasive ability through reduced production of matrix metalloproteinases (MMP-2 and MMP-9) and cell motility in head and neck cancer cell lines. Furthermore, inostamycin abrogated the stimulatory effect of VEGF (vascular endothelial growth factor) on growth and migration activities of endothelial cells by targeting extracellular signal-regulated kinase-cyclin D1 and p38 pathways, respectively. Because inostamycin has both antiproliferative and anti-invasive abilities, inhibition of phosphatidylinositol synthesis could be a potent therapeutic strategy for head and neck cancer as the 'cancer dormant therapy', i.e. a therapeutic concept to prolong 'time to treatment failure' or 'time to progression'.

Objectives: To examine the association between hearing handicap and depressive symptoms in older community-dwelling Japanese. DESIGN: Community-based cohort study. Setting: Kurabuchi Town, Gunma Prefecture, Japan. Participants: Five hundred eighty residents (261 men, 319 women) aged 65 and older without depressive symptoms. Measurements: In a baseline examination performed in 2005/06, participants answered the 10-item screening version of the Hearing Handicap Inventory for Elderly (HHIE-S). They were divided into two groups according to their scores: a group with no hearing handicap (HHIE-S scores of ≤8) and a hearing handicap group (HHIE-S scores of ≥10). The Geriatric Depression Scale was used to identify depressive symptoms in face-to-face home visit interviews conducted in 2008, and the association between hearing handicap and depressive symptoms was assessed using logistic regression. Results: The incidence of depressive symptoms was 19.6% in the group with a hearing handicap and 8.0% in the group without a hearing handicap. When compared with the subjects without hearing handicap, subjects with a hearing handicap had a multiadjusted odds ratio of depressive symptoms of 2.45 (95% confidence interval=1.26-4.77). The association remained significant even when hearing impairment measured with pure-tone audiometry was added to the multiadjusted model. Conclusion: A hearing handicap can predict future depressive symptoms in older community-dwelling people.

kull-base and parapharyngeal tumors require intricate treatments due to its anatomic complexity, variations in histological type, and the site often involves the presence of critical blood vessels and nerves. Diagnostic imaging and fine-needle aspiration cytology are thus essential. We report a case of skull-base meningioma extending to the parapharyngeal space in which we made a definitive diagnosis by biopsy (as grade I) and took a wait-and-see approach. A 52-year-old woman had complained of a headache since June 2006 and was seen in the neurology department at our hospital in July. A tumor from around the left jugular foramen to parapharyngeal space was revealed by magnetic resonance imaging (MRI) and she was referred for consultation to the neurosurgical department and our department. It was difficult to establish the diagnosis from the clinical manifestation and diagnostic images due to the tumor's complicated anatomy, therefore it was confirmed by biopsy instead of cytology. It can be said that biopsy is useful to determine therapeutic measures for the skull-base meningioma because it is less invasive and can verify a histological type compared with the complete removal of the tumor.

Introduction. Deep neck infection is a life-threatening condition, and intravenous antibiotic therapy is preferable in the early stages of the disease. However, in the advanced stages, surgical drainage should be performed. Although several surgical treatment strategies are available, it is necessary to standardize treatment according to the patient's general condition and history. Case presentation. We report the case of a 68-year-old man with a deep neck abscess and with severe diabetes mellitus and inflammation. Computed tomography identified a deep neck infection extending from the level of the epipharynx to that of the hyoid bone. We performed surgical drainage by transnasal endoscopy. The patient exhibited no evidence of either recurrent disease or post-surgical complications within 30 months of follow-up. Conclusions. This case report provides evidence that transnasal endoscopic drainage should be recommended as a standard approach in patients with a deep neck abscess and with a severe general condition, diabetes mellitus, and inflammation.

Conclusion: These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. Objective: Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. Materials and methods: A total of 25 adult guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. Results: Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.

Introduction: Treatments for acute peripheral vertigo have not been well investigated. The most suitable drug for controlling acute vertigo should suppress both vertigo and accompanying nausea. The purpose of this study was to evaluate the effect of four different drugs on acute peripheral vertigo: (A) hydroxyzine hydrochloride (25 mg, i.v.); (B) 0. 5% metoclopramide (2 ml, i.v.); (C) sodium bicarbonate (40 ml, i.v.); and (D) a cocktail of diphenhydramine hydrochloride (30 mg) and dyprophylline (26 mg) (both i.m.). Methods: Forty-two patients with acute peripheral vertigo (average age: 59. 5 ±18.1 years) with spontaneous nystagmus were assigned to four treatment groups (A-D, above). Patients with central vertigo and vestibular neuritis were excluded. The number of patients in each group was as follows: A, n= 11; B, n=ll; C, n=ll; and D, n=9. Patients were instructed to evaluate their subjective symptoms of nausea and vertigo before and 30 minutes after drug treatment. They rated the severity of their symptoms on a 0-to-10 scale, with 10 representing the most severe symptoms and 0 a lack of symptoms. Results: Group A patients (hydroxyzine hydrochloride; 25 mg, i.v.) reported the highest level of relief from vertigo and nausea after drug treatment, whereas group C (sodium bicarbonate; 40 ml, i.v.) and D (diphenhydramine hydrochloride (30 mg)-dyprophylline (26 mg) cocktail; i.m.) patients reported only the slight relief of these symptoms. Group B patients (0. 5% metoclopramide; 2 ml, i.v.) experienced partial symptom relief; their vertigo remained unchanged. Thus, hydroxyzine hydrochloride (A) was the most effective in controlling both nausea and vertigo, whereas sodium bicarbonate (C) and diphenhydramine hydrochloride and dyprophylline (D) only slightly suppressed vertigo and nausea. Metoclopramide (B) only suppressed nausea. Conclusions: Hydroxyzine hydrochloride (A) was the most suitable for treating acute peripheral vertigo. Doctors should be familiar with the contraindications of these drugs. Some of these drugs may potentially be used in combination to control the symptoms of acute vertigo more effectively.

Introduction: Patients suffering from ear discomfort are commonly encountered in the department of otolaryngology. If various clinical examinations do not reveal any objective findings, then the patients are referred to the department of internal medicine or psychiatry. Psychotherapy is recommended in some cases. This paper describes the successful administration of autogenic training in a patient suffering from ear discomfort due to major depression. Case presentation: We present a case of intractable depression that was successfully treated with a combination of psychotherapy, administered by a clinical psychologist, and high-dose antidepressant. The patient was a 36-year-old female with hearing discomfort in her left ear. In 2003, she experienced insomnia and an appetite loss, and her condition was diagnosed as major depression along with an avoidant personality disorder. Her depression has not been improved with antidepressant treatment for 3 years in department of psychosomatic medicine. She was referred to our department because of ear discomfort in her left ear. There was no abnormality in her physical examinations. She wanted to be treated in department of otorhinolaryngology. We increased the dose of fluvoxamine maleate up to 200 mg/day, and introduced cognitive therapy and autogenic training by a clinical psychologist. Eventually, her depressive state as well as the hearing complaint was markedly alleviated. Conclusions: Autogenic training can be a viable and acceptable treatment option for patients who fail to respond to other therapies. This case emphasizes the importance of autogenic training as a method to control physical symptom of depression.

Otosclerosis is an otological disease that typicaly causes conductive hearing loss. This disease is an important clinical entity since hearing impairment in these case can be dramatically improved by surgery. In this review paper, we review recent research into the pathophysiology of otosclerosis and summarize clinical features, audiometry and diagnostic imaging examinations in 160 ears with otosclerosis that we treated surgically in our department.

Introduction: Anxiety and depression are closely related to mental and physical disease prognosis. This makes it important to know anxiety and depression levels in patients with physical or mental disorders who visited the department of otorhinolaryngology. We evaluated the anxiety and depression levels in such patients using a hospital anxiety and depression scale (HADS). Methods: Subjects were 67 individuals whose degree of anxiety and depression was decided on HADS. Subjects were then divided into 4 groups-group I, no anxiety or depression; group II, depression alone, group III, anxiety alone, and group IV, both anxiety and depression. We then looked at the relationship between these results and their major perceived problems. Results: Groups I had 39 subjects II 7, III 8, and IV 13. Anxiety and depression were correlated (r= 0. 56; p<0. 0001). 90% of subjects reported dizziness, tinnitus, or throat discomfort. Those with throat discomfort had the highest anxiety score, while those with anxiety most commonly reported dizziness. Conclusions: Our results suggest that subjects may have anxiety and/or depression. The evaluation of anxiety and depression based on physical complaints may be difficult for otorhinolaryngologists, but it is important to do so where possible to increase the focus on the subject's physical illness and perceived problems.

Nestin is an intermediate filament expressed in immature cells in the CNS including neural stem/progenitor cells, reactive astrocytes and immature neurons in lesser amounts after injury. Nestin expression in the nucleus ambiguus following vagal nerve injury was studied using nestin-EGFP transgenic rats. We confirmed that EGFP immunoreactivity was evident at 6 h to 8 days in ipsilateral nucleus ambiguus after nerve transection. Properties of these cells were examined immunohistochemically. These EGFP-immunoreactive cells were immunoreactive for Tuj1 and Hu, and exhibited ChAT activity. However, no immunoreactivity for GFAP or CNPase was observed. In normal development, the level of KCC2 expression is known to increase with maturation of neurons. In our study, decreased KCC2 expression was observed in nestin-EGFP-positive cells within the nucleus ambiguus on the lesioned side compared with the contralateral side. These EGFP-immunoreactive cells were immunonegative for BrdU. This is the first study to demonstrate the expression of a neural stem/progenitor cell-enriched marker, Nestin, in the nucleus ambiguus after vagal nerve injury. The present findings suggest that mature motoneurons are an origin of these Nestin-positive cells, which are induced after injury. Mature neurons in the nucleus ambiguus may thus have the potential to juvenilize after vagal/recurrent laryngeal nerve injury.

The electrocautery snare has been widely used in gastroenterology and to remove bronchial and urinary bladder lesions, but rarely in head and lesion electrocautery. Since October 2006, we have used this instrument to treat 17 head and neck granuloma, papilloma, cyst, and cancer lesions under local or general anesthesia. Lesions were localized in the larynx, oropharynx, hypopharynx, or tracheostoma. The snare was used through a rhinolaryngovideoscope in most cases with a current of 15-30 watts produced by an electrosurgical generator. All procedures were easy, quick and successful, with minimal bleeding. No severe adverse effects were seen in any of our cases. The electrocautery snare was extremely useful in treating pedunculated lesions and in removing epiglottic cysts with a clear margin after excision of the mass without bleeding. Our results indicate the electrocautery snare to be useful and safe in treating selected head and neck lesion cases.

We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in adults. All were women in their 20s and 30s. Three cases had severe hearing impairment characterized by hearing loss at every frequency; 2 cases had profound hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6 cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual disturbance. All 6 cases were initially diagnosed as having idiopathic sudden sensorineural hearing loss; all subsequently received steroid therapy. Three cases were not diagnosed as being psychogenic in origin until otoacoustic emissions and auditory brain responses were performed. Although the presence of distinctive clinical features (age, gender, and past history) is important for suspecting psychogenic hearing loss, objective audiological tests such as otoacoustic emissions are essential for diagnosing some cases. Compared to the existing reports of similar cases, our cases had a poorer prognosis (only 2 cases were cured).

Objectives: The medial wall of the maxillary sinus, or the bony buttress, plays an important role in supporting the orbital floor. Since part of the bony buttress is removed in the inferior meatal antrostomy (IMA), it is expected that the IMA makes the orbital floor likely to develop serious fractures in traumatic situations. We conducted the present study to elucidate the effect of the IMA on the vulnerability of the orbital floor. Methods: After producing CAD (Computer Assisted Design) models simulating twelve skulls, we performed simulation antrostomy for each of the twelve CAD models in both the middle meatus and the inferior meatus. According to the site of the antrostomy, the models were categorized as the MMA (middle meatal antrostomy) or IMA groups. We then applied an impact on the orbital region of each model. Using the finite element method, we calculated the area of the orbital wall fracture induced by the impact. Then we compared the area of the orbital wall fractures between the MMA and IMA groups. Results: The orbital wall fracture areas were significantly greater in the IMA group than in the MMA group. Conclusions: The patients who underwent IMA are likely to develop serious orbital fractures if their orbits receive traumatic impacts. Hence, surgeons should be prudent in their indications for IMA.

Background: There have been inconsistent results regarding the contribution of the connexin family of genes to tumor cell proliferation. Materials and Methods: We aimed to clarify the role of connexin 30 (Cx30), by transfecting three kinds of vectors that express either full length Cx30 (Cx30-Full), Cx30 devoid of C-terminal region (Cx30-DelC) or Cx30 C-terminal region (Cx30-CT), in HSC-4, a head-and-neck cancer cell line. Results: Transfected Cx30-Full was localized on the plasma membrane, while Cx30-DelC and Cx30-CT was expressed in the cytoplasm or circumnuclear sites. We studied the effect on the growth rate followed by immunostaining with anti-Ki-67 (MIB-1). The MIB indices of HSC-4 cells transfected with Cx30-Full and Cx30-DelC, but not Cx30-CT were shown to be significantly higher than that of the controls. Conclusion: Our results demonstrated that Cx30 enhanced the proliferation of HSC-4 cells and the proliferating activity was considered to be achieved without the transport of the protein onto the plasma membrane.

CONCLUSION: These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. OBJECTIVE: Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. MATERIALS AND METHODS: A total of 25 adult guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. RESULTS: Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.

Objective: The purpose of this study was to assess laryngeal function after supracricoid laryngectomy. Study Design: Case series. Subjects and Methods: Supracricoid laryngectomy (SCL) has been performed in our institution for 24 selected patients with laryngeal cancer since December 2000. Reconstruction was performed through cricohyoidoepiglottopexy for 23 patients and cricohyoidopexy for 1 patient. Seven patients had ipsilateral arytenoid removal, and 15 patients underwent SCL as salvage surgery. A retrospective chart review was performed to assess postoperative speech and swallowing function. Stroboscopy and/or fiberscopy of the neoglottis were used to assess postoperative speech kinetics. Acoustic parameters were measured to evaluate vocal function, and several questionnaires were used to evaluate postoperative quality of life (QOL). Results: In the absence of postoperative complications, stoma closure and normal diet intake were achieved 1 month after surgery. The neoglottis comprises the arytenoid(s), epiglottis, and pyriform sinus mucosa. Several different combinations of vibrating regions were observed among patients during phonation. Although vocalization sounded rough and breathy, vocal communication was possible with little inconvenience. Conclusion: Acceptable functional recovery and tolerable QOL can be achieved after SCL.

Objectives: Prevention of relapse, or postoperative dislocation, of the fixed zygoma is necessary to achieve optimal results in the treatment of zygoma fractures. Assuming that the occurrence of intensified stresses on mastication at the screw-bone interface (SBI) constitutes the essential cause of the relapse, we evaluated the stresses for three different fixation methods-fixation at the frontal process (FP), inferior orbital rim (IOR), and zygomatico-maxillary buttress (ZMB). Methods: We used 10 computer-aided design (CAD) models simulating zygoma fractures in the experiment. For each CAD model, we fixed the fractured zygoma with four screws and one mini-plate at the FP, IOR, or ZMB. After applying a 5.5 kg force simulating mastication, we calculated the intensity and distribution patterns of the stresses occurring at the SBIs of the fixation screws using the finite element method. Thereby, we evaluated dynamic stability of the fixed zygoma for each of the three fixation methods. Results: Greater stresses occur at the SBIs with IOR fixation than at those with FP and ZMB fixation. Although the stresses occurring at the SBIs on mastication demonstrated evenly distributed patterns with the FP and ZMB fixation, the stresses demonstrated concentration on one screw with the IOR fixation. Conclusions: The fixed zygoma is more likely to cause relapse with the IOR fixation than with the FP or ZMB fixation. Hence, in performing zygoma fixation at the IOR, care should be taken to minimize the likelihood of postoperative relapse that is caused by skewed distribution of the stresses on the fixation screws.

In order to evaluate feeding and swallowing functions in patients recruited by the Nutrition Support Team (NST), we investigated their underlying diseases, primary departments, age distribution, nutrition administration routes, and feeding and swallowing, The survey was conducted on 66 cases determined to be suffering from malnutrition based on screening of all hospitalized patients. The elderly aged 65 or over accounted for 86 percent of all cases. Neurological disorders were the most prevalent type of disease, affecting 29 percent of all cases. Oral feeding accounted for 40 percent, and supplemental nutrition for 60 percent of all cases. The incidence of aspiration was 66 percent. Forty-two percent of all cases did not involve oral administration. Feeding and swallowing functions were more seriously affected in cases of respiratory and neuromuscular diseases as compared with other diseases. Our findings suggest that in order to carry out safe oral nutrition, medical staff must evaluate the individual patient's feeding and swallowing functions.